P1059: COMPARATIVE EFFICACY OF FEDRATINIB AND PACRITINIB FOR THE TREATMENT OF MYELOFIBROSIS IN PATIENTS WITH LOW PLATELET COUNTS: A SIMULATED TREATMENT COMPARISON STUDY
Authors: G. Tremblay, P. Daniele, P. Abraham, S. Rose, A. McBride
Journal: HemaSphere (2022)

Background: Myelofibrosis (MF) is a Philadelphia chromosome-negative myeloproliferative neoplasm with an estimated prevalence of 4–6/100,000 persons in the United States (US). Among intermediate- to high-risk patients, Janus kinase 2 (JAK2) inhibitors are the primary treatment for MF. Fedratinib was approved by the US Food and Drug Administration (FDA) based on the results of the JAKARTA trials (NCT01437787; NCT01523171), and a new drug application for pacritinib was submitted to the FDA for the treatment of MF in patients with severe thrombocytopenia. Aims: To assess the comparative efficacy of fedratinib and pacritinib in patients with MF and thrombocytopenia (platelets < 100 × 109/L), in the absence of head-to-head clinical trials, an indirect treatment comparison (ITC) was conducted. Methods: According to the results of a systematic literature review, JAKARTA, JAKARTA2, and PERSIST-2 (NCT01773187) trials formed the basis of the ITC. A pooled analysis data set was developed using individual patient-level data from the fedratinib 400-mg arms of JAKARTA and JAKARTA2 including patients with platelets < 100 × 109/L. Published summary data from the pacritinib 200-mg arm of PERSIST-2 served as the comparator. Simulated treatment comparisons (STCs) were used to compare spleen volume reduction (SVR) ≥ 35% while adjusting for mutually reported baseline patient characteristics such as age, sex, Dynamic International Prognostic Scoring System status, Eastern Cooperative Oncology Group (ECOG) performance status (PS), JAK2 V617F mutation status, prior ruxolitinib exposure, and laboratory tests. Final adjustment models were selected based on fit statistics and the literature review. Indirect relative risk (RR) was estimated with 95% confidence intervals (CIs) using unanchored naive ITC (unadjusted) and STC (adjusted) methodologies. A naive ITC was also conducted for the subgroup of patients who received ruxolitinib in prior lines of therapy. In addition, a sensitivity analysis was conducted to evaluate the impact of differential median baseline platelet counts, which PERSIST-2 did not report. Using the full pooled population of the JAKARTA trials, outcomes were simulated at 3 median baseline platelet counts (25, 50, and 75 × 109/L) and compared using similar methodology to the main analysis. Results: The main analysis suggests that fedratinib is associated with a greater proportion of SVR ≥ 35% than pacritinib. According to the naive ITC, fedratinib was numerically favored over pacritinib in terms of SVR ≥ 35% (RR, 1.67 [95% CI, 0.94–2.97]). After the STC adjustment, fedratinib was statistically favored relative to pacritinib for SVR ≥ 35% (RR, 1.76 [95% CI, 1.00–3.10]). The naive ITC results were similar for patients who had received ruxolitinib in prior lines of therapy (RR, 2.82 [95% CI, 1.02–7.82]). Results of the platelet-count-adjusted sensitivity analysis showed a significant difference in favor of fedratinib with respect to SVR ≥ 35%. Differential baseline platelet count had minimal impact on the ITC results, with similar RRs regardless of simulated median baseline platelet count. Image:Summary/Conclusion: This analysis used a population-adjusted ITC to assess the comparative efficacy of pacritinib and fedratinib in patients with MF and thrombocytopenia. Following population adjustment, fedratinib was associated with a greater proportion of patients achieving SVR ≥ 35% than pacritinib. Further real-world evidence studies should be conducted to assess the effectiveness of these treatments in clinical settings.